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| Status |
Public on Aug 06, 2018 |
| Title |
Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5 year-old child with severe pulmonary influenza at 2 years. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not interferon-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient’s cells is much narrower than that of control cells; however, induction of a subset of interferon-stimulated gene transcripts remains detectable. In vitro, the patient’s cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus, and respiratory syncytial virus. These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.
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| Overall design |
Total of 72 samples, 38 samples from primary fibroblasts and 34 samples from EBV-transformed B cells, were analyzed using paired-end RNA sequence data. Out of 38 samples from primary fibroblasts, 3 control samples are paired with no stimulation vs IFNa2b stimulation. Out of 34 samples from B-cells, 3 control samples are paired with no stimuliion vs IFNa2b stimulation. In addition to healthy control subjects, patients with AR complete STAT1 (STAT1 -/-) or STAT2 (STAT2 -/-) deficiency were analyzed for comparison.
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| Contributor(s) |
Hernandez N, Melki I, Jing H, Habib T, Huang S, Danielson J, Kula T, Drutman S, Belkaya S, Rattina V, Lorenzo-Diaz L, Boulai A, Rose Y, Kitabayashi N, Rodero M, Dumaine C, Blanche S, Lebras M, Leung MC, Mathew LS, Boisson B, Zhang S, Boisson-Dupuis S, Chaussabel D, Notarangelo LD, Elledge S, Ciancianelli M, Abel L, Zhang Q, Marr N, Crow Y, Su H, Casanova J |
| Citation(s) |
30143481 |
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| Submission date |
Jul 25, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Tanwir Habib |
| E-mail(s) |
thabib@sidra.org
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| Organization name |
Sidra Medicine
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| Street address |
Al Luqta Street
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| City |
Doha |
| ZIP/Postal code |
26999 |
| Country |
Qatar |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA482784 |
| SRA |
SRP155182 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE117637_GEO_normalized_log.xls.gz |
6.9 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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